Predicting recovery from paraplegia after thoracoabdominal aneurysm repair

Introduction: Spinal cord ischaemia (SCI) is perhaps the most feared complication post-thoracoabdominal aortic aneurysm (TAAA) repair. We examined cellular and proteomic changes in cerebrospinal fluid (CSF) and related these to neurological outcome. Methodology: Patients undergoing TAAA repair with CSF drainage were recruited. CSF was collected pre-operatively and 24-hourly until drain removal. Daily neurological examinations were performed. CSF cell/protein content was characterised by flow cytometry and tandem-mass-tag labelled proteomics respectively. Results: CSF was analysed from 52 patients (age: 70.27 +/-11.4 years; 66% male; Crawford Type I (10.8%) II (29.2%), III (26.2%), IV (30.8%), V (3.1%); open (n=9), total endovascular (n=43). 12 patients developed SCI; 5 remaining permanently-paraplegic. All permanently paraplegic patients had undergone endovascular repair. CSF from Permanent-paraplegics contained more CD45+ leucocytes (P<0.0001). Levels of aquaporin-4, an astrocyte osmoreceptor essential in maintaining blood/spinal cord barrier integrity, was >7-fold higher in permanently-paraplegic CSF versus recovered patients (P=0.0008). Patients with CSF aquaporin-4 >15ng/ml predicted permanent paraplegia with a specificity of 100%, and were more likely to have pathological spinal cord swelling on T2-weighted MRI (P<0.05). Conclusion: The present study is the largest analysis of CSF post-TAAA repair in-man. Our results suggest that permanent paraplegia is associated with shedding of bound-AQP4 from parenchymal cord into CSF and a breakdown of blood/spinal-cord barrier. This breakdown allows the migration of oedema/leucocytes into the cord and may explain the pathogenesis of irreversible paraplegia after TAAA repair. The CSF signature we have described may prove useful in predicting prognosis after SCI and identifies AQP4 as a potential therapeutic target.